Treatment of Refractory/Relapsed Non-Hodgkin Lymphoma With TriCAR-T_CD19

Phase 1

• Conditions: Non-hodgkin Lymphoma,B Cell

• Registration Number: NCT03497533
• Lead Sponsor: Timmune Biotech Inc.

Brief Summary

This is a single arm, open-label, single-center, phase 1/2 study, to determine the safety and efficacy of TriCAR-T-CD19, an autologous tri-functional anti-CD19 chimeric antigen receptor (CAR)-positive T cell therapy, in refractory/Relapsed Non-Hodgkin Lymphoma (NHL).

Detailed Description

The tri-functional anti-CD19 chimeric antigen receptor contains an anti-CD19 scFv, a PD-L1 blocker, and a cytokine complex, enabling the TriCAR-T-CD19 to simultaneously targeting the CD19 positive NHL，blocking the inhibitory PD-L1 signal and stimulating T/NK cell activation and expansion.

Study Timeline

• Study First Submitted: 2018-02-11
• Study First Submitted QC: 2018-04-10
• Study First Posted: 2018-04-13
• Study Start: 2018-08-03
• Status Verified: 2019-09
• Last Update Submitted: 2019-09-05
• Last Update Posted: 2019-09-06
• Primary Completion: 2020-12-31
• Study Completion: 2020-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

1. All subjects must personally sign and date the consent form before initiating any study specific procedures or activities;
2. All subjects must be able to comply with all the scheduled procedures in the study;
3. Histologically or cytologically confirmed CD19 positive non-Hodgkin lymphoma;
4. Chemotherapy-refractory disease, defined as one or more of the following: Relapsed in 6 months after most recent therapy; Progressive disease in the standard R-CHOP or CHOP chemotherapy; Disease progression or relapsed in ≤12 months of ASCT (must have biopsy proven recurrence in relapsed subjects); If salvage therapy is given post-ASCT, the subject must have had no response to or relapsed after the last line of therapy.
5. No available standard therapy;
6. At least one measurable lesion per revised IWG Response Criteria;
7. Aged 18 to 68 years;
8. Expected survival ≥12 weeks;
9. Eastern cooperative oncology group (ECOG) performance status of ≤2;
10. Systematic usage of immunosuppressive drug or corticosteroid must have been stopped for more than 4 weeks;
11. All other treatment induced adverse events must have been resolved to ≤grade 1;
12. Laboratory tests must fulfill the following criteria: ANC ≥ 1000/uL, HGB >70g/L, Platelet count ≥ 50,000/uL, Creatinine clearance ≤1.5 ULN, Serum ALT/AST ≤2.5 ULN, Total bilirubin ≤1.5 ULN (except in subjects with Gilbert's syndrome);
13. Female must be not pregnant during the study.

Exclusion Criteria

1. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years;
2. History of allogeneic stem cell transplantation;
3. Prior other CAR therapy or other genetically modified T cell therapy;
4. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment;
5. Subjects with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases;
6. Lactating women;
7. Active infection with hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive);
8. Subjects need systematic usage of corticosteroid;
9. History of any gene therapy;
10. Subjects need systematic usage of immunosuppressive drug;
11. Known history of infection with HIV;
12. Planed operation, history of other related disease, or any other related laboratory tests restrict patients for the study;
13. Other reasons the investigator think the patient may not be suitable for the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Safety (Incidence of treatment-related adverse events as assessed by CTCAE v4.0)	30 Days	Incidence of treatment-related adverse events as assessed by CTCAE v4.0

Secondary Outcome Measures

Name	Time	Method
Partial response rate [PR] (Partial response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)	12 months	Partial response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma
Duration of Response （The time from response to relapse or progression）	12 months	The time from response to relapse or progression
Progression Free Survival（The time from the first day of treatment to the date on which disease progresses.）	12 months	The time from the first day of treatment to the date on which disease progresses.
Overall Survival（The number of patient alive, with or without signs of cancer）	24 months	The number of patient alive, with or without signs of cancer
Complete response rate[CR] (Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma)	12 months	Complete response rate per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma

Trial Locations

Locations (1)

Hunan Provincial People's Hospital; 🇨🇳 Changsha, Hunan, China